Clinical Features Of Colorectal Cancer Research Articles

Clinical significance of serum IGFBP-3 in colorectal cancer.

BackgroundIGF‐binding protein 3（IGFBP‐3）has previously been identified as tumor marker. The present study aimed to investigate the clinical significance of serum IGFBP‐3 in colorectal cancer (CRC).MethodsSerum was collected from 70 CRC patients and 50 healthy volunteer controls. Serum IGFBP‐3 and carcinoembryonic antigen (CEA) levels were measured using electrogenerated chemiluminescence immunoassay and compared between groups. Relationships between serum IGFBP‐3 level and the clinical characteristics of CRC were also analyzed. A receiver operator characteristic (ROC) curve was plotted to investigate diagnostic efficacy of serum IGFBP‐3 and CEA, respectively, for CRC. Data were analyzed using SPSS 13.0.ResultsSerum IGFBP‐3 levels in CRC were lower than those of controls (4.68 [3.56, 5.77] vs 5.44 [4.77, 6.10] µg/mL, P < 0.05). Furthermore, serum IGFBP‐3 levels were higher in early cancer stages (I and II) than those of advanced stages (III and IV) (4.78 [3.92, 5.49] vs 3.77 [2.65, 4.59] µg/mL, P < 0.05). In addition, patients with lymph node metastasis absent had elevated serum IGFBP‐3 levels than those of patients with lymph node metastasis present (4.73 [3.92, 5.72] vs 4.11 [2.45, 4.83] µg/mL, P = 0.02). Finally, ROC curve indicated that serum IGFBP‐3 had a better diagnostic power for CRC than CEA. When serum IGFBP‐3 and carcinoembryonic antigen were used together to detect CRC, the AUC was 0.949, with a sensitivity of 75% and a specificity of 90%.ConclusionsSerum IGFBP‐3 might be a potential biomarker for CRC.

Clinical Characteristic of Young Indonesian Colorectal Cancer Patients: A Preliminary Study

&lt;p&gt;Introduction: Colorectal cancer (CRC) is generally a disease of persons aged above 40 year-old. Controversies still exist regarding clinical characteristics of CRC in young persons. The aim of this study is to know the clinical characteristics of young CRC patients in Siloam General Hospital, Karawaci, Banten.&lt;/p&gt;&lt;p&gt;Material And Methods: A total of 14 patients with diagnosis of CRC from December 2013 to January 2014 in Siloam General Hospital, Karawaci, Banten were studied cross – sectionally. The symptoms and signs, family history of cancer, diabetes, location of mass were collected and evaluated.&lt;/p&gt;&lt;p&gt;Results: There were 5 (35.7%) cases of CRC patients aged below 40 year-old (young patients) and 9 (64.3%) above 40 years-old (old patients). The most common symptom was constipation followed by bloody diarrhea i.e. 57.1% and 42.9% consecutively. Constipation occurred in 2 and 6 young and old patients consecutively and in 3 and 3 young and old patients consecutively. In young patients, 2 (14.2%) had a history of cancer in the family compared to none in the old patients. According to the location of tumor in the colon 4 (28.5%) were in ascending colon with 2 and 2 in young and old patients consecutively, 3 (21.7%) were in descending colon with 2 and 1 in young and old patients consecutively, 8 (57.1%) were in rectum with 2 and 6 in young and old patients consecutively. One young patient had diabetes, and one other young patient had positive &lt;em&gt;Clostridium difficile&lt;/em&gt; antigen and toxin.&lt;/p&gt;&lt;p&gt;Conclusion: Approximately 35.7% cases CRC patient in our hospital was of young patients. Two patients were having family history of cancer. The location of mass was not specific for young CRC patients.&lt;/p&gt;&lt;strong&gt;&lt;em&gt;Key words: colorectal cancer, young patients&lt;/em&gt;&lt;/strong&gt;

Uc.338 targets p21 and cyclin D1 via PI3K/AKT pathway activation to promote cell proliferation in colorectal cancer.

Ultraconserved regions (UCRs) are 481 segments that have been strictly conserved among many mammalian species for hundreds of years. Their transcribed products belong to long non‑coding RNAs and are closely involved in the progression of various tumors. uc.338 has been reported to promote cell proliferation in hepatocellular and lung cancers. However, the role of uc.338 in colorectal cancer (CRC) proliferation remains unclear. In the present study, we first detected the expression of uc.338 in human tissues and analyzed the relationship between uc.338 expression and clinical features of CRC. We then investigated the biological function of uc.338 in CRC proliferation invitro and invivo. Finally, we explored the potential mechanism by which uc.338 promotes the proliferation of CRC cells. Our results indicated that uc.338 was upregulated in CRC tissues and higher uc.338 expression was associated with a larger tumor size, deeper invasion, increased lymph node metastasis and poorer prognosis. Further investigations invivo and invitro revealed that uc.338 could promote proliferation and cell cycle G1/S transition, and might target p21 downregulation and cyclin D1 upregulation via the PI3K/AKT pathway in CRC cells. Thus, our findings suggested that uc.338 acts as an oncogene by promoting proliferation in CRC cells, and could become a novel target for CRC detection and therapy.

Comprehensive analysis of a long noncoding RNA-associated competing endogenous RNA network in colorectal cancer.

PurposeThis study was aimed to develop a lncRNA-associated competing endogenous RNA (ceRNA) network to provide further understanding of the ceRNA regulatory mechanism and pathogenesis in colorectal cancer (CRC).Patients and methodsExpression profiles of mRNAs, lncRNAs, and miRNAs, and clinical information for CRC patients were obtained from The Cancer Genome Atlas. The differentially expressed mRNAs, lncRNAs, and miRNAs (referred to as “DEmRNAs”, “DElncRNAs”, and “DEmiRNAs”, respectively) were screened out between 539 CRC samples and 11 normal samples. The interactions between DElncRNAs and DEmiRNAs were predicted by miRcode. The DEmRNAs targeted by the DEmiRNAs were retrieved according to TargetScan, miRTar-Base, and miRDB. The lncRNA–miRNA–mRNA ceRNA network was constructed based on the DEmiRNA–DElncRNA and DEmiRNA–DEmRNA interactions. Functional enrichment analysis revealed the biological processes and pathways of DEmRNAs involved in the development of CRC. Key lncRNAs were further analyzed for their associations with overall survival and clinical features of CRC patients.ResultsA total of 1,767 DEmRNAs, 608 DElncRNAs, and 283 DEmiRNAs were identified as CRC-specific RNAs. Three hundred eighty-two DEmiRNA–DElncRNA interactions and 68 DEmiRNA–DEmRNA interactions were recognized according to the relevant databases. The lncRNA–miRNA–mRNA ceRNA network was constructed using 25 DEmiRNAs, 52 DEmRNAs, and 64 DElncRNAs. Two DElncRNAs, five DEmiRNAs, and six DEmRNAs were demonstrated to be related to the prognosis of CRC patients. Four DElncRNAs were found to be associated with clinical features. Twenty-eight Gene Ontology terms and 10 Kyoto Encyclopedia of Genes and Genomes pathways were found to be significantly enriched by the DEmRNAs in the ceRNA network.ConclusionOur results showed cancer-specific mRNA, lncRNA, and miRNA expression patterns and enabled us to construct an lncRNA-associated ceRNA network that provided new insights into the molecular mechanisms of CRC. Key RNA transcripts related to the overall survival and clinical features were also found with promising potential as biomarkers for diagnosis, survival prediction, and classification of CRC.

Expressions of IGF-1, ERK, GLUT4, IRS-1 in metabolic syndrome complicated with colorectal cancer and their associations with the clinical characteristics of CRC

Epidemiological data have revealed that colorectal cancer (CRC) risk is increased in patients with Metabolic syndrome. To explore the expressions of IGF-1, ERK, GLUT4, IRS-1 in MS patients with CRC and their associations with the clinical characteristics of CRC. We investigated the expressions of IGF-1, ERK, GLUT4 and IRS-1 in greater omental adipose tissues of 168 MS patients with/without CRC, 85 CRC patients without MS and 98 healthy controls by RT-PCR, and analyzed the relationships between their expressions and clinical characteristics of CRC. The expression levels of IGF-1 and ERK in MS patients with/without CRC were higher while the expression levels of GLUT4 were lower compared with CRC patients without MS and healthy controls (P< 0.01). The expression levels of IGF-1 and ERK in MS patients with CRC were higher while expression levels of GLUT4 were lower compared to MS patients without CRC (P< 0.01). Expression levels of ERK, IGF-1, GLUT4 were associated with clinical characteristics of CRC, including tumor size, distant metastasis and advanced stages (III/IV) (P< 0.05). Expressions of IGF-1, ERK and GLUT4 in greater omental adipose tissues might be useful biomarkers and predictive targets in the diagnosis of CRC.

TNF-α -308 A allele is associated with an increased risk of distant metastasis in rectal cancer patients from Southwestern China.

Tumor necrosis factor-α (TNF-α), an important factor in systematic inflammation, is reportedly involved in several cancer types. The TNF-α -308 G>A (rs1800629) polymorphism in the promoter region influences TNF-α production. The association between TNF-α -308 G>A polymorphism and colorectal cancer (CRC) is not fully understood, especially the connections between TNF-α -308 G>A polymorphism and clinical features of CRC. In this study, TNF-α -308 G>A polymorphism was genotyped in 1140 individuals with or without CRC from Southwestern China. In case-control studies, we found no association between TNF-α -308 G>A polymorphism and CRC risk. Analysis of the correlations between TNF-α -308 G>A polymorphism and clinical features of CRC revealed that TNF-α -308 A allele was associated with higher body mass index (BMI) larger tumor size, and distant tumor metastasis in all CRC patients. Notably, rectal cancer (a subtype of CRC) patients with TNF-α -308 A allele had a very high risk of distant tumor metastasis [odds ratio (OR) = 4.481; 95% confidence interval (CI): 2.072–9.693; P = 0.00025]. The association between TNF-α -308 A allele and distant tumor metastasis remained even significant after adjusting all clinical characteristics (OR = 7.099; 95% CI: 2.482–20.301; P = 0.000256) in rectal cancer patients. Our results suggested that TNF-α -308 A allele was significantly associated with distant tumor metastasis in rectal cancer patients.

Abstract IA03: Lessons from colorectal cancer

Abstract Many of the fundamental tenets of cancer genetics have their origins in the study of colorectal cancer (CRC). This is, at least in part, due to several clinical features of CRC that make it a particularly attractive and amenable to study in humans. Some of these key features include the relative abundance of CRC and precursor adenomas in the general population, the ease of identifying and collecting adenomas through routine screening colonoscopies, the existence of well recognized histopathological classifications with defined clinical implications and the long standing description of several well defined inherited predispositions. As a result, studies in CRC have often proven to be seminal in defining the role of somatic mutations and germline variations in the initiation progression and resistance of human cancer. Moreover, studies of CRC have proven to be influential beyond the aforementioned areas helping to define the roles of diet, inflammation and the microbiome in human cancer and providing new paradigms for the prevention and management of cancer. How these findings inform our understanding of CRC and cancer in general will be discussed with special emphasis on emerging topics highlighted in this conference. Citation Format: Kenneth W. Kinzler. Lessons from colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA03.

SnoRNAs are involved in the progression of ulcerative colitis and colorectal cancer

Background and aimEmerging evidences indicate that small nucleolar RNAs (snoRNAs) are important regulatory molecules involved in various pathophysiological processes including inflammation and cancer. In the current study, we investigate whether snoRNAs dysregulate in colorectal cancer (CRC) and intestinal inflammation and contribute the pathogenesis of CRC. MethodsWe analyzed the snoRNAs expression profile in CRC patients by GeneChipR Array and validated candidate snoRNAs expression in 44 CRC tissues, as well as in 28 ulcerative colitis (UC) and 28 healthy controls using reverse transcription quantitative polymerase chain reaction. Furthermore, we analyzed the correlation between snoRNAs expression and clinical characteristics of CRC and evaluated the diagnosis and differentiation efficiencies of the snoRNAs in CRC and UC. ResultsThe expression of snoRA15, snoRA41 displayed increased, whereas snoRD33 was down-regulated in CRC compared with matched non-cancerous tissues. When compared to healthy control, the three snoRNAs are all upregulated in lesion tissue of UC and CRC, which showed an increasingly trend from healthy control to UC and CRC. ConclusionsThe identified three snoRNAs might contribute the carcinogenesis of colorectal cancer and involve in the progress from chronic intestinal inflammation to malignant tumor.

Knowledge and Awareness about Colorectal Cancer and Its Screening Guidelines among Doctors in Al Ahsa, Eastern Province, Kingdom of Saudi Arabia

INTRODUCTION: Cancer is a major public health problem. Worldwide, colorectal cancer (CRC) is a leading cause of deaths due to cancer in both men and women. Among, Saudi men, CRC is the most common malignancy while it is the third most common among Saudi women. Over, two decades the incidence and deaths due to CRC have been steadily increasing in Saudi Arabia. Regular and timely screening has the potential in reducing the incidence and deaths due to colorectal cancer. The present study is conducted to evaluate the knowledge and awareness about colorectal cancer and its screening among the doctors.OBJECTIVES: To measure the frequency of knowledge and awareness about colorectal cancer and its screening guidelines among doctors in Al-Ahssa.METHODS: A questionnaire based survey of the doctors (Specialists &amp; residents), working in different hospitals and primary health centers under the Ministry of Health in Al Ahssa region, Eastern province, KSA. Knowledge and awareness about colorectal cancer and its screening among the doctors is evaluated.RESULTS: Over 80% of the doctors knew, screening reduces deaths due to CRC. Only 60% were aware about the risk factors and less than 50% knew the clinical features of CRC. About 60% doctors agreed Colonoscopy is gold standard screening test. While, less than 60% knew the ideal age to initiate screening and the actual interval of screening tests in the standard risk and high-risk population. Fewer than 25% doctors were aware about the American cancer society recommended screening guidelines. Majority of the doctors expressed keen interest to know and receive information about CRC and its screening guidelines. CONCLUSIONS: Regular and timely screening reduces deaths due to CRC. There is a need for improving knowledge and awareness of doctors about CRC and its screening. Awareness among the doctors improves uptake of screening by the general and high-risk population.

Gankyrin sustains PI3K/GSK-3β/β-catenin signal activation and promotes colorectal cancer aggressiveness and progression.

High levels of angiogenesis, metastasis and chemoresistance are major clinical features of colorectal cancer (CRC), a lethal disease with a high incidence worldwide. Aberrant activation of Wnt/β-catenin pathway contributes to CRC progression. However, little is known about regulatory mechanisms of the β-catenin activity in cancer progression. Here we report that Gankyrin was markedly upregulated in primary tumor tissues from CRC patients and was associated with poor survival. Moreover, we demonstrated that overexpressing Gankyrin promoted, while knockdown of Gankyrin impaired, the aggressive phenotype of proliferation, angiogenesis, chemoresistance and metastasis of CRC cells both in vitro and in vivo. Importantly, we found a unique molecular mechanism of Gankyrin in CRC cells signaling transduction, that regulated the cross-talk between PI3K/Akt and Wnt/β-catenin signaling pathways, sustaining PI3K/GSK-3β/β-catenin signal activation in CRC. Therefore, these findings not only reveal a mechanism that promotes aggressiveness and progression in CRC, but also provide insight into novel molecular targets for antitumor therapy in CRCs.

Клинические особенности колоректального рака, осложненного инвазией в мочевую систему

Клинические особенности колоректального рака, осложненного инвазией в мочевую систему

Quantitative detection of the tumor-associated antigen large external antigen in colorectal cancer tissues and cells using quantum dot probe.

The large external antigen (LEA) is a cell surface glycoprotein that has been proven to be highly expressed in colorectal cancer (CRC) as a tumor-associated antigen. To evaluate and validate the relationship between LEA expression and clinical characteristics of CRC with high efficiency, LEA expression levels were detected in 85 tissue blocks from CRC patients by quantum dot-based immunohistochemistry (QD-IHC) combined with imaging quantitative analysis using quantum dots with a 605 nm emission wavelength (QD605) conjugated to an ND-1 monoclonal antibody against LEA as a probe. Conventional IHC was performed in parallel for comparison. Both QD-IHC and conventional IHC showed that LEA was specifically expressed in CRC, but not in non-CRC tissues, and high LEA expression was significantly associated with a more advanced T-stage (P<0.05), indicating that LEA is likely to serve as a CRC prognostic marker. Compared with conventional IHC, receiver operating characteristic analysis revealed that QD-IHC possessed higher sensitivity, resulting in an increased positive detection rate of CRC, from 70.1% to 89.6%. In addition, a simpler operation, objective analysis of results, and excellent repeatability make QD-IHC an attractive alternative to conventional IHC in clinical practice. Furthermore, to explore whether the QD probes can be utilized to quantitatively detect living cells or single cells, quantum dot-based immunocytochemistry (QD-ICC) combined with imaging quantitative analysis was developed to evaluate LEA expression in several CRC cell lines. It was demonstrated that QD-ICC could also predict the correlation between LEA expression and the T-stage characteristics of the cell lines, which was confirmed by flow cytometry. The results of this study indicate that QD-ICC has the potential to noninvasively detect rare circulating tumor cells in clinical samples in real clinical applications.

P0022 Clinical characteristics of young Indonesian colorectal cancer patients: A preliminary study

Background Colorectal cancer is generally a disease of people aged above 40 years. Controversies still exist regarding the clinical characteristics of colorectal cancer in young people. The aim of this study is to know the clinical characteristics of young patients with colorectal cancer at the Siloam General Hospital, Karawaci, Banten. Methods 14 patients with a diagnosis of colorectal cancer from December 2013, to January 2014, in Siloam General Hospital were studied cross-sectionally. The symptoms and signs, family history of cancer, diabetes, and location of mass were collected and evaluated. Findings Five (35.7%) cases of colorectal cancer were in patients aged below 40 years (young patients) and nine (64.3%) cases were in patients above 40 years (old patients). The most common symptom was constipation and bloody diarrhoea, occurring in 57.1% of young patients and in 42.9% of old patients. Constipation occurred in two young patients and six old patients, and bloody diarrhoea occurred in three young patients and three old patients. Two (14.2%) young patients had a history of cancer in the family, whereas none of the old patients had a family history of cancer. Regarding location of tumour in the colon, four (28.5%) patients had a tumour in the ascending colon; two of the cases in young patients and the remaining two cases in old patients. Three (21.7%) patients had a tumour in descending colon; two cases were in young patients and one was in an old patient. Eight (57.1%) patients had a tumour in the rectum; two of the cases were in young patients and six cases were in old patients. One young patient had diabetes, and one other young patient had positive Clostridium difficile antigen and toxin. Interpretation Approximately 35.7% cases of colorectal cancer (CRC) in our hospital were in young patients. Two patients had a family history of cancer. The location of mass was not specific for young patients with colorectal cancer.

Clinical characteristics of colorectal cancer as a second primary malignancy.

e14691 Background: Advances in cancer screening and treatment in the past 20 years have improved cancer specific survival rates, raising questions regarding second primary malignancies and the path...

Correlation between tumor engraftment in patient-derived xenograft models and clinical outcomes in colorectal cancer patients.

Despite numerous studies involving patient-derived xenograft (PDX) models, few studies have investigated the relationship between the ability of the tumor to engraft (tumorigenicity) and the clinical features of colorectal cancer (CRC). The aim of this study was to determine whether tumorigenicity correlates with clinical outcomes of CRC patients. We included 241 CRC patients who underwent radical surgery from 2010 to 2013. PDX models were established by implanting tumor fragments obtained from these patients into the subcutaneous layer of immunodeficient mice. Xenografts were successfully established from 62.2%. Successful engraftment was associated with advanced stage (p < 0.001) and moderate/poor differentiation (p = 0.029). Three-year disease-free survival (DFS) rates were lower for patients with tumorigenicity (p = 0.011). In stage III patients, tumorigenicity was an independent predictor of poor DFS (p = 0.034). In addition, mutation of TP53 was most frequently detected in stage III patients with tumorigenicity. Two models of stage IV disease without KRAS mutations showed high sensitivity to EGFR-targeted agents, while none of the models with KRAS mutations showed high sensitivity. In conclusion, PDX models may provide an effective preclinical tool for predicting cancer progression and could be used to further genomic and pharmacologic research on personalized treatments.

Epidemiological and Clinical Characteristics of Colorectal Cancer in Hypothyroidism

Introduction: Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer deaths in the United States. Overall, CRC incidence and mortality rates are higher in men and highest in African Americans, followed by Caucasians. Few studies demonstrated a preventive role of thyroid hormone (TH) in the development and invasiveness of CRC. Methods: In a retrospective cohort, we identified 48 patients with CRC and hypothyroidism (cases). The patients were sex-matched with 174 patients who had CRC without hypothyroidism (controls). Data were collected for depth of tumor invasion, lymphovascular invasion, tumor location, staging (TNM), histologic type, level of differentiation, and positive-to-total lymph node ratio. Results: Females constituted 83.3% of cases. Mean age at diagnosis in case and control was (74.7±11.05 years, 76.3±12.28 years, respectively; p=-0.25). The other demographic variables were similar in 2 groups except race, with the patients in the cases being overwhelmingly Caucasian (91.6% versus 54.0% in control; p<0.001). In the unadjusted regressions, patients with hypothyroidism were more likely to have deep tumor invasions (OR 0.874; 95% CI -0.01, 1.76). In the adjusted regressions, Hispanic patients with hypothyroidism had significantly lower odds of high stage than Caucasian patients (OR -7.007; 95% CI -13.47, -0.55). The point estimates for hypothyroidism and the interaction with age at diagnosis for the TNM stage (OR 10.222; 95% CI 0.91, 19.53; OR -0.138; 95% CI -0.26, -0.02, respectively) and for lymphovascular invasion, (OR 8.618; 95% CI 0.09, 17.15; OR -0.120; 95% CI -0.23, -0.01, respectively), imply that at age 74 years or younger at diagnosis of CRC, hypothyroidism raises the odds of having higher TNM stage and lymphovascular invasion. Conclusion: Cyclin D1 is an oncogenic cyclin, which is frequently overexpressed in CRC and Wnt, signaling pathway is involved in development sporadic CRC. TH-bound thyroid receptors (TRs) inhibit the transcription of cyclin D though the Tcf/Lef-1 site, which is positively regulated by Wnt signaling pathway. In patients with hypothyroidism, colorectal tumor exhibit reduced TRB1 expression. This may be the basis for why our study demonstrated that female Caucasian patients with hypothyroidism are more likely to have worse tumor characteristics of CRC at age less than 74 years.

Significant association between IL23R and IL17F polymorphisms and clinical features of colorectal cancer

Th17cells are involved in inflammatory and autoimmune diseases. These cells may be involved in pathological processes mainly producing pro-inflammatory cytokines. Recently, it was shown that the IL23/IL17 pathway plays an important role in the development of inflammatory bowel disease. In general, genes encoding cytokines are genetically polymorphic and polymorphisms in genes IL23R el IL17F were shown associated with susceptibility to Crohn's disease and ulcerative colitis which in their turn are considered as risk factors for developing colorectal cancer (CRC). Our approach is to study IL17F and IL23R polymorphisms as risk factor associated with CRC in the Tunisian population in patients and healthy controls. Interesting, we noted a significant association between IL17F and IL23R polymorphisms and tumor location (p=0.0001 and p=0.049, respectively), tumor histology (p=0.007 and p=0.049, respectively) and tumor architecture (p=0.0000000001 and p=0.07, respectively) in CRC patients. We also showed a significant association of IL17F variant with an increased risk of TNM stage III/IV (p=0.007), showing an increased risk of advanced stage. Finally, we observed a positive link between IL17F polymorphism and CRC patients with lymph nodes (p=0.0000000001) and metastasis (p=0.00000009). However, we found no evidence to support a significant association between IL17F and IL23R polymorphisms and colorectal cancer susceptibility. Our findings suggest that IL17F and IL23R polymorphisms were significantly associated with clinical features variables. The IL17F cytokine appear to be involved in the control of tumor growth and invasion of gastrointestinal tumors. IL17 and IL23 polymorphisms or those of their receptors as important determinants of susceptibility to colorectal cancer are still subject to questioning.

Rab27b is a potential predictor for metastasis and prognosis in colorectal cancer.

Objective. Rab27b is reported to correlate with cancer development and progression. However, the association between Rab27b expression and the clinical characteristics of colorectal cancer (CRC) is barely investigated. Methods. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 113 CRC cases were performed to explore the relationship between Rab27b expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were executed to evaluate the prognosis of CRC. Results. The results demonstrated that the expression levels of Rab27b mRNA and protein were significantly higher in CRC tissues than that in matched noncancerous tissues (P < 0.05). Rab27b protein expression in CRC was statistically correlated with serum CEA level (P = 0.004), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), and TNM stage (P = 0.001). Cox multifactor analysis and Kaplan-Meier method suggested that higher Rab27b protein expression (P = 0.041) and tumor differentiation (P = 0.001) were significantly associated with the overall survival of CRC patients. Conclusions. The data indicated that higher expression of Rab27b was observed in CRC tissues and Rab27b may be identified as a useful predictor of metastasis and prognosis for CRC.

Hepatic steatosis is associated with lower incidence of liver metastasis from colorectal cancer

Both hepatic steatosis (HS) and colorectal cancer (CRC) are conditions associated with metabolic syndrome. The liver is the most frequent site of distant metastasis of CRC; however, the impact of HS on the incidence of liver metastasis of CRC is not clearly defined. Then, the correlation with the presence or absence of HS was analyzed. A total of 604 CRC patients receiving curative surgical resection who had a preoperative non-enhanced computed tomography (CT) were enrolled. The mean attenuation values (in Hounsfield units) of the liver and spleen were obtained on a plain CT slice, and the patients with liver-spleen attenuation ratio lower than 1.1 were objectively defined as HS. The clinicopathological features of these patients were analyzed, and the association between HS and the clinical features of CRC was examined. Sixty-three (10.4%) among the 604 patients were diagnosed as HS. Recurrence-free survival (RFS) and hepatic RFS, but not extrahepatic RFS, were significantly higher in the group with HS (p = 0.04 and p = 0.006). However, this effect was not evident in the group of patients with obesity, defined as body mass index > 25.0. Among the stage I~III cases, HS was significantly associated with lower hepatic, but not extrahepatic, RFS. Moreover, absence of HS was an independent risk factor for hepatic RFS (p = 0.003). Metastases of CRC are less frequent in fatty liver. Steatosis may be an unfavorable microenvironment for metastatic formation in the liver.

Decreased expression of repulsive guidance molecule member A by DNA methylation in colorectal cancer is related to tumor progression

Previous studies have shown decreased expression of repulsive guidance molecule member A (RGMa) in colorectal cancer. However, the relationship between the expression levels and promoter DNA methylation status of RGMa and the clinical characteristics of colorectal cancer has not been previously reported. Here, we investigated the expression of RGMa by immunohistochemistry, real-time PCR and western blotting and analyzed the methylation status of the RGMa promoter using Sequenom's MassARRAY platform in colorectal cancer tissues and adjacent normal colorectal tissues. The results showed that RGMa expression was decreased in cancer tissues compared with adjacent normal tissues (p<0.01). Furthermore, a tendency for decreased expression in tumor tissues was observed from Dukes' stage A to stage D (p<0.01). In addition, significantly higher levels of hypermethylation in promoter regions of RGMa were observed in colorectal cancer tissues, compared with those in adjacent normal colorectal tissues (p<0.01). Moreover, the methylation levels of RGMa in tumor tissues were significantly increased in Dukes' stage C and D compared with Dukes' stage A and B (p<0.01). Our results indicate that RGMa expression and promoter methylation status are closely related to colorectal cancer genesis and progression. Determination of the expression level and methylation frequency of RGMa in colorectal cancer tissues may have benefit for early diagnosis and for evaluating patient prognosis.